Pulmonary Vascular Dilatation Research Articles

Chronic Hypoxemia Inadvanced Liver Diseases: Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is one of the pulmonary complications from liver disease with or without cirrhosis. The prevalence of HPS varies from 4% to 47% in patients with liver cirrhosis. We present a case of chronic progressive dyspnea in an 18-year-old man with a history of chronic liver disease. Diagnosing can be particularly challenging, especially in cases involving prolonged dyspnea and comorbidities. Following thorough investigations, the patient's condition was attributed to a rarer condition: severe hepatopulmonary syndrome. Contrast-enhanced echocardiography with agitated saline is the gold standard for diagnosing pulmonary vascular dilatation which is the hallmark of HPS. There is currently no medical therapy approved for HPS. Oxygen therapy is recommended for patients with severe hypoxemia.

Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod

Hepatopulmonary syndrome (HPS) is characterised by a defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, suppresses vasodilation by reducing nitric oxide (NO) production. We investigated the role of S1P in patients with HPS and the role of fingolimod as a therapeutic option in an experimental model of HPS. Patients with cirrhosis with HPS (n= 44) and without HPS (n= 89) and 25 healthy controls were studied. Plasma levels of S1P, NO, and markers of systemic inflammation were studied. In a murine model of common bile duct ligation (CBDL), variations in pulmonary vasculature, arterial oxygenation, liver fibrosis, and inflammation were estimated before and after administration of S1P and fingolimod. Log of plasma S1P levels was significantly lower in patients with HPS than in those without HPS (3.1 ± 1.4 vs. 4.6 ± 0.2; p <0.001) and more so in severe intrapulmonary shunting than in mild and moderate intrapulmonary shunting (p <0.001). Plasma tumour necrosis factor-α (76.5 [30.3-91.6] vs. 52.9 [25.2-82.8]; p= 0.02) and NO (152.9 ± 41.2 vs. 79.2 ± 29.2; p= 0.001) levels were higher in patients with HPS than in those without HPS. An increase in Th17 (p <0.001) and T regulatory cells (p <0.001) was observed; the latter inversely correlated with plasma S1P levels. In the CBDL HPS model, fingolimod restored pulmonary vascular injury by increasing the arterial blood gas exchange and reducing systemic and pulmonary inflammation, resulting in improved survival (p= 0.02). Compared with vehicle treatment, fingolimod reduced portal pressure (p <0.05) and hepatic fibrosis and improved hepatocyte proliferation. It also induced apoptotic death in hepatic stellate cells and reduced collagen formation. Plasma S1P levels are low in patients with HPS and even more so in severe cases. Fingolimod, by improving pulmonary vascular tone and oxygenation, improves survival in a murine CBDL HPS model. A low level of plasma sphingosine-1-phosphate (S1P) is associated with severe pulmonary vascular shunting, and hence, it can serve as a marker of disease severity in patients with hepatopulmonary syndrome (HPS). Fingolimod, a functional agonist of S1P, reduces hepatic inflammation, improves vascular tone, and thus retards the progression of fibrosis in a preclinical animal model of HPS. Fingolimod is being proposed as a potential novel therapy for management of patients with HPS.

Relationship Between Pulmonary Vascular Dilatation and Clinical Symptoms on Chest Computed Tomography in Patients with Confirmed COVID-19

Introduction: Chest computed tomography (CT) is important in establishing a diagnosis, including detecting pulmonary vascular dilatation as a radiological feature of COVID-19, and consequently in providing comprehensive treatment. This study aimed to analyze the relationship between pulmonary vascular dilatation and clinical symptoms on chest CT in patients with confirmed COVID-19.&#x0D; Methods: This retrospective cross-sectional study was conducted at the Radiology Department of Dr. Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital, Makassar, Indonesia, from July to September 2021 in a total of 231 patients with confirmed COVID-19. The chi-squared correlation test was used to analyze the data, with p-values of &lt;0.05 considered significant.&#x0D; Results: Pulmonary vascular dilatation was observed in 31 (37.8%) of the 82 patients with confirmed COVID-19 with mild-to-moderate clinical symptoms and in 51 (69.8%) of the 73 patients with confirmed COVID-19 with severe-to-critical clinical symptoms. The incidence of pulmonary vascular dilatation increased in the patients with confirmed COVID-19 with severe-to-critical clinical symptoms. The chief complaints of most patients were cough, shortness of breath, and fever. In the patients with mild-to-moderate clinical symptoms, the most common chief complaint was cough (n=53; 64.63%), while in those with severe-to-critical clinical symptoms, the most common chief complaint was shortness of breath (n=60; 82.19%).&#x0D; Conclusions: Based on chest CT findings, pulmonary vascular dilatation is related to clinical symptoms in patients with confirmed COVID-19.

A Brief Review on Hepatopulmonary Syndrome

Hepatopulmonary Syndrome is defined as decreased saturation of arterial oxygen due to dilatation of pulmonary vasculature in the presence of portal hypertension or advanced liver disease. In the year 1977, hepatopulmonary syndrome was first proposed based on the clinical findings and autopsy. In the patients with chronic liver disease, pulmonary manifestations like pulmonary vascular dilatation were observed in the autopsies.In the liver disease setting, dyspnea is usually present in the patient. The onset of dyspnea is gradual and aggravates by exertion. Most of the patients are asymptomatic during the early stages. This review article mainly focuses on the epidemiology, pathophysiology, clinical manifestations, diagnosis along with the treatment and management. A multidisplinary approach is required with the involvement of hepatologists, pulmonologists, primary clinicians, addiction medicine specialist, transplant surgeons and clinical pharmacists in the management of HPS.

55Identification of celastramycin as a novel therapeutic agent for pulmonary arterial hypertension - high-throughput screening of 5,562 compounds

Abstract Background Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) accompanying increased production of inflammatory factors and adaptation of mitochondrial metabolism to a hyperproliferative state. However, at present, since all the drugs in clinical use target pulmonary vascular dilatation, they may not be so effective for patients with advanced PAH. Purposes We aimed to discover a novel drug for PAH that inhibits PASMC proliferation. Methods In the first screening, we examined 5,562 compounds from our original library using high-throughput screening system to discover a compound that inhibits proliferation of PASMCs from PAH patients (PAH-PASMCs). In the second screening, we performed concentration-dependent assays and counter assays with PAH-PASMCs and PASMCs from healthy donors. We also performed apoptosis assays and mechanistic analysis for inflammation, reactive oxygen species (ROS), and mitochondrial function. Results We found that celastramycin, a benzoyl pyrrole-type compound originally found in a bacteria extract, inhibited the proliferation of PAH-PASMCs in a dose-dependent manner with minimal effects on PASMCs from healthy donors. Moreover, celastramycin inhibited proliferation with minimal increase in apoptosis and low rate of cell death. Then, we synthesized 25 analogues of celastramycin, and finally selected the lead compound that significantly inhibited proliferation of PAH-PASMCs and reduced cytosolic ROS levels. Mechanistic analysis demonstrated that celastramycin reduced the protein levels of hypoxia-inducible factor-1α, which was abnormally activated in PAH-PASMCs and impaired aerobic metabolism, and nuclear factor-κB, which induces pro-inflammatory signals, in PAH-PASMCs compared with vehicle controls, leading to reduced secretion of inflammatory cytokines. Importantly, celastramycin treatment reduced the ROS levels in PAH-PASMCs with increased protein levels of NF-E2-related factor 2 (Nrf2), a master regulator of cellular response against oxidative stress. Furthermore, celastramycin treatment improved mitochondrial energy metabolism with recovered mitochondrial network formation in PAH-PASMCs. We also discovered that celastramycin-mediated effects on these transcriptional modulators could be regulated by zinc finger C3H1 domain-containing protein, which is a binding partner of celastramycin. Finally, celastramycin treatment ameliorated pulmonary hypertension in three experimental animal models of PH in mice and rats, accompanied by reduced inflammatory changes in the lungs. Conclusions These results indicate that celastramycin ameliorates pulmonary hypertension through inhibition of excessive proliferation of PAH-PASMCs, for which its anti-inflammatory and beneficial effects on mitochondrial energy metabolism may be involved. Thus, celastramycin could be a novel drug for PAH as it exerts anti-proliferative effects on PAH-PASMCs.

Identification of Celastramycin as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) accompanying increased production of inflammatory factors and adaptation of the mitochondrial metabolism to a hyperproliferative state. However, all the drugs in clinical use target pulmonary vascular dilatation, which may not be effective for patients with advanced PAH. We aimed to discover a novel drug for PAH that inhibits PASMC proliferation. We screened 5562 compounds from original library using high-throughput screening system to discover compounds which inhibit proliferation of PASMCs from patients with PAH (PAH-PASMCs). We found that celastramycin, a benzoyl pyrrole-type compound originally found in a bacteria extract, inhibited the proliferation of PAH-PASMCs in a dose-dependent manner with relatively small effects on PASMCs from healthy donors. Then, we made 25 analogs of celastramycin and selected the lead compound, which significantly inhibited cell proliferation of PAH-PASMCs and reduced cytosolic reactive oxygen species levels. Mechanistic analysis demonstrated that celastramycin reduced the protein levels of HIF-1α (hypoxia-inducible factor 1α), which impairs aerobic metabolism, and κB (nuclear factor-κB), which induces proinflammatory signals, in PAH-PASMCs, leading to reduced secretion of inflammatory cytokine. Importantly, celastramycin treatment reduced reactive oxygen species levels in PAH-PASMCs with increased protein levels of Nrf2 (nuclear factor erythroid 2-related factor 2), a master regulator of cellular response against oxidative stress. Furthermore, celastramycin treatment improved mitochondrial energy metabolism with recovered mitochondrial network formation in PAH-PASMCs. Moreover, these celastramycin-mediated effects were regulated by ZFC3H1 (zinc finger C3H1 domain-containing protein), a binding partner of celastramycin. Finally, celastramycin treatment ameliorated pulmonary hypertension in 3 experimental animal models, accompanied by reduced inflammatory changes in the lungs. These results indicate that celastramycin ameliorates pulmonary hypertension, reducing excessive proliferation of PAH-PASMCs with less inflammation and reactive oxygen species levels, and recovered mitochondrial energy metabolism. Thus, celastramycin is a novel drug for PAH that targets antiproliferative effects on PAH-PASMCs.

Sindrom Hepatopulmoner

Hepatopulmonary syndrome (HPS) is an important complication of liver disease on pulmonary organ; characterized by the triad of liver disease, pulmonary vascular dilatation, and oxygenation defect. Clinical signs and symptoms include dyspnea, platypnea, orthodeoxia, cyanosis, and clubbing finger. The underlying patophysiology involves abnormal vasodilation and angiogenesis in the pulmonary vascular bed, which leads to ventilation-perfusion mismatch, diffusion limitation to oxygen exchange, and arteriovenous shunting. This disorder is thought to be linked to liver cell injury, which stimulates release of endothelin-1 and results in increased expression of endothelin receptors on pulmonary endothelial cells, leading to upregulation of endothelial-nitric-oxide-synthase (eNOS) and subsequent increased production of nitric oxide (NO), ultimately causing vasodilation. Laboratory studies to establish diagnosis includes blood gas analysis and echocardiography, supported by radiology and pulmonary vascular cathetherization. Despite accumulated knowledge about the pathogenesis of HPS, currently there is still no established medical therapy, and liver transplantation remains the definitive treatment for this syndrome. Supportive therapy consists oflong term oxygen administration to prevent desaturation and alleviate dyspnea.

Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2≤ 70mmHg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging andexplanted livers were reviewed. CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.

Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study.

Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient>15mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36±0.02, 1.02±0.18, 2.86±0.77, and 6.56±1.46 EU/mL, p<0.001) and LBP (7026±3336, 11,445±1247, 11,947±1164, and 13,791±2032ng/mL, p=0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83±0.17, 2.62±0.22, 3.69±0.28, and 4.29±0.34pg/mL, p<0.001), demonstrating a significant difference between each grade (p<0.05). HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS.

Hepatopulmonary syndrome and liver transplantation: the review and a case report

Hepatopulmonary syndrome is a liver disease complication characterized by the clinical triad of an advanced chronic liver disease, a pulmonary vascular dilatation, and a reduced arterial oxygenation (hypoxemia: PaO2 less than 70 mm Hg at rest) in the absence of intrinsic cardiopulmonary disease. Precapillary vasodilatation, intrapulmonary angiogenesis and hyperdynamic circulation lead to arteriovenous shunting and reduced gas diffusion. In case of detecting macroscopic shunts, the pulmonary artery branch embolization could be performed. However, the hepatopulmonary syndrome can be cured nowadays by means of liver transplantation only. A 5-year survival in these patients is about 70%. The observed mortality is the highest during the surgery or early after, especially in patients with PaO2 lower than 50 mm Hg. It ranges from 8.5 to 29%. A prolonged oxygenation support is often required after liver transplantation using invasive or non-invasive ventilation, or even extracorporeal membrane oxygenation. In this review, we have focused on the recent advances in this field as described in available literature and have presented a case report of successful liver transplantation in a patient with a severe hepatopulmonary syndrome.

Hepatopulmonary Syndrome: A Commonly Missed Complication of Chronic Liver Disease

Case of a 65-year-old man with medical history of hypertension and cirrhosis secondary to Hepatitis C, who was initially consulted to gastroenterology service due to intermittent loose and blood tinged stools for which he was scheduled for a colonoscopy. On the procedure day he was found with a peripheral O2 saturation of 88% at room air, improving to 99% with nasal cannula. Hepatopulmonary syndrome was suspected, but prior to starting work up, patient was admitted under Internal Medicine service due to progressive dyspnea and multiple syncopal episodes. During admission a pulmonary scintigraphy was performed reporting abnormal tracer concentration in several extrapulmonary organs, highly suggestive of a right-to-left shunt. Pulmonary service evaluated patient and noted that after exercise testing disease severity interpretation had changed from moderate to very severe. Upon discharge patient was requiring continuous oxygen supplementation. Subsequently, cardiology service performed contrast echocardiogram with agitated saline in which contrast was seen to enter the left atrium 6 beats after first entering the right atrium, confirming hepatopulmonary syndrome. Patient was referred to the liver transplant center, where he was placed on transplant list with MELD exception. Hepatopulmonary syndrome is caused by a defect in arterial oxygenation due to pulmonary vascular dilatation in the setting of liver disease. Contrast-enhanced transthoracic echocardiography with saline is the most practical method to detect pulmonary vascular dilatation. Dyspnea at exertion or at rest, although non-specific, is the most common presenting finding. Prevalence of this syndrome ranges from 5%-32% although no prospective studies are available. Liver transplantation is the only treatment with documented success. This case serves to illustrate the importance of maintaining a keen eye on subtle symptoms that a patient with chronic liver disease may develop and which may usually be put off as part of the disease per se. Patients with chronic liver disease should have at least peripheral oximetry obtained in each routine visit and arterial blood gases should be obtained if there is dyspnea. Early suspicion of hepatopulmonary syndrome in cirrhotic patients is important in order to provide them a prompt work up which will definitely expedite the liver transplant process before the syndrome progresses and excludes them as candidates.

Síndrome hepatopulmonar

Hepatopulmonary syndrome is characterized by the presence of liver disease, pulmonary vascular dilatations, and arterial hypoxemia. It is usually associated with cirrhosis of any origin, but has been described in other liver diseases, both acute and chronic, and not always associated with portal hypertension. The gold standard method to detect pulmonary vascular dilations is contrast enhancement echocardiography with saline and is essential for the diagnosis of hepatopulmonary syndrome. These dilatations reflect changes in the pulmonary microvasculature (vasodilatation, intravascular monocyte accumulation, and angiogenesis) and induce a ventilation/perfusion mismatch, or even true intrapulmonary shunts, which eventually trigger hypoxemia. This syndrome worsens patients’ prognosis and impairs their quality of life and may lead to the need for liver transplantation, which is the only effective and definitive treatment. In this article, we review the etiological, pathophysiological, clinical and therapeutic features of this syndrome.

Aggravation of hepatopulmonary syndrome after sildenafil treatment in a patient with coexisting portopulmonary hypertension.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are complications of portal hypertension and cirrhosis. Their pathophysiological mechanisms clearly differ. HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation. In contrast, PPHTN is predominantly due to excessive pulmonary vasoconstriction and vascular remodeling, but is rarely associated with hypoxia. We report a case of a patient who had both HPS and PPHTN at the time of presentation. HPS was aggravated after sildenafil administration for the treatment of PPHTN. We demonstrated increased amount of intrapulmonay shunt after sildenafil challenge by using agitated saline contrast transthoracic echocardiography.

A RARE CASE OF CYANOSIS AND CLUBBING –LIVER INDUCED VASCULAR DISORDER OF LUNG

Abstract:The hepatopulmonary syndrome (HPS) is under recognized complication of chronic liver disease. Hepatopulmonary syndrome has three components: liver disease, pulmonary vascular dilatation, and a defect in oxygenation. If hypoxemia and dyspnea develop in these patients in the absence of known intrinsic cardiopulmonary disorder, the hepatopulmonary syndrome must be considered. Clinical features include digital clubbing, cyanosis, spider neavi. It is a rare complication of liver disease of varied etiology and indicates a poor prognosis. We are reporting a case of severe clubbing of fingers associated with severe cyanosis and chronic liver disorder in a very young girl to highlight that other causes also should be thought of in addition to cyanotic congenital heart disease in such a young age.

Interstitial Lung Disease in Patients with Hepatopulmonary Syndrome: A Case Series and New Observations

Hepatopulmonary syndrome (HPS) is characterized by impaired oxygenation due to pulmonary vascular dilatation in patients with end-stage liver disease. At our center, we identified 29 patients who were listed for liver transplantation (LT) with a model for end-stage liver disease exception for HPS between 2001 and 2012. Five of these patients were found to have concurrent interstitial lung disease (ILD). The chest high-resolution computed-tomography demonstrated ground-glass opacities and subpleural reticulation, most consistent with nonspecific interstitial pneumonia (NSIP). All four of our patients who underwent LT experienced prolonged hypoxemia postoperatively, with one surgery-related death. However, the three surviving patients had eventual resolution of their hypoxemia with no evidence of ILD progression. In conclusion, we report a high prevalence of ILD, most consistent with NSIP, among patients with HPS. Although there may be increased perioperative risks, the finding of ILD in patients with HPS should not be considered an absolute contraindication to LT.

Hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that induces severe hypoxaemia. Considering the favourable long-term survival of HPS patients as well as the reversal of the syndrome with a functional liver graft, HPS is now an indication for orthotopic liver transplantation (OLT). Consequently, blood gas analysis and imaging techniques should be performed when cirrhotic patients present with shortness of breath as well as when OLT candidates are placed on the transplant waiting list. If the arterial partial pressure of oxygen (PaO2) is more than 10.7 kPa when breathing room air, HPS can be excluded and no other investigation is needed. When the PaO2 when breathing room air is 10.7 kPa or less, contrast-enhanced echocardiography should be performed to exclude pulmonary vascular dilatation. Lung function tests may also help detect additional pulmonary diseases that can contribute to impaired oxygenation. When contrast-enhanced echocardiography is negative, HPS is excluded and no follow-up is needed. When contrast-enhanced echocardiography is positive and PaO2 less than 8 kPa, patients should obtain a severity score that provides them with a reasonable probability of being transplanted within 3 months. In mild-to-moderate HPS (PaO2 8 to 10.6 kPa), periodic follow-up is recommended every 3 months to detect any further deterioration in PaO2. Although no intraoperative deaths have been directly attributed to HPS, oxygenation may worsen immediately following OLT due to volume overload and postoperative infections. Mechanical ventilation is often prolonged with an extended stay in the ICU. A high postoperative mortality (mostly within 6 months) is observed in this group of patients in comparison to non-HPS patients. However, the recovery of an adequate PaO2 within 12 months after OLT explains the similar outcome of HPS and non-HPS patients following OLT over a longer time period.

Transition from Hepatopulmonary Syndrome to Portopulmonary Hypertension: A Case Series of 3 Patients

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are the two major pulmonary vascular complications of liver disease. While HPS is characterized by low pulmonary vascular resistance, PPHTN is defined by the presence of elevated pulmonary vascular resistance. Given these seemingly opposing pathophysiologic mechanisms, these conditions were traditionally felt to be mutually exclusive. In this series, we present three patients with severe hepatopulmonary syndrome who had spontaneous resolution of their HPS with the subsequent development of PPHTN. To our knowledge, this is the largest case series presented of this phenomenon in nontransplanted patients. One proposed mechanism for the occurrence of this phenomenon involves dysregulation of the same vascular signaling pathway, which may lead to both pulmonary vascular dilatations and pulmonary arterial remodeling in the same patient. Another theory involves the possible differential binding of endothelin-1, a vasoactive signaling peptide that induces vasoconstriction when bound to receptor A and vasodilation when bound to receptor B. Although the mechanisms for this phenomenon remain unclear, it is important to be vigilant of this phenomenon as it may change the patient's overall treatment plan, especially in regard to appropriateness and timing of liver transplant.

The effects of flavanoid on the treatment of hepatopulmonary syndrome

PurposeHepatopulmonary syndrome is an arterial oxygenation disorder brought about by advanced liver failure and pulmonary vascular dilatations. The reason why hypoxia develops in hepatopulmonary syndrome depends on the broadening of perialveolar capillary veins. Our study aims to investigate the effects of Flavanoid on hepatopulmonary syndrome through its inhibition of nitric oxide.MethodsThree groups, each having 8 rats, were formed within the scope of our study. Group I (the control group) only received laparatomy, group II received choledoch ligation, and group III was administered Flavanoid (90% flavonoid diosmin, 10% flavonoid hesperidin) following choledoch ligation. The rats were administered Flavanoid at week two following choledoch ligation. The rats' livers and lungs were examined histopathologically following a five-week follow-up and the perialveolar vein diameters were measured. Arterial blood gases and biochemical parameters were evaluated.ResultsIt was seen that fibrosis and oxidative damage in the liver with obstructive jaundice as well as hypoxia with pulmonary perialveolar vein sizes were significantly lower than the other group with cirrhosis formed through the administration of Flavanoid.ConclusionWe have concluded that Flavanoid administration might be useful in the treatment of hypoxia in hepatopulmonary syndrome and the delay of cirrhosis contraction.

Hepatopulomnary Syndrome among Cirrhotic Patients in Upper Egypt: Prevalence, Clinical Presentations and Laboratory Features

Background: The prevalence of Hepatopulmonary Syndrome (HPS) ranges from 5 to 32% from livertransplantation centers. Egypt is considered as one of the highest countries in prevalence and incidence of bilharizial peri-portal fibrosis and Hepatitis C Virus (HCV) induced liver cirrhosis. Clinical, radiological and laboratory features of HPS were not widely assessed. Objectives: To determine the prevalence, clinical features and laboratory features of HPS among Egyptian cirrhotic patients. Patients and Methods: Our study included 570 cirrhotic patients. Arterial blood gases analysis, chest X-ray, pulmonary function tests and transthoracic contrast echocardiography for detection of pulmonary vasodilatation were done for patients with partial pressure of arterial O2<80 mmHg. Also, clinical and laboratory features were assessed. Diagnostic criteria of HPS in cirrhotic patients include arterial hypoxemia and pulmonary vascular dilatation on contrast enhanced echocardiography. Results: The prevalence of HPS among patients with liver cirrhosis was 4.2%. Patients with HPS had more severe cirrhosis, as determined by advanced Child-Pugh Grade. The presence of dyspnea, platypnea, clubbing, and orthodoxia was significantly higher in patients with HPS when compared to cirrhotic patients (P value<0 .001). In HPS, right pleural effusion and bilateral basal shadows were the commonest radiological findings (20.8% while chest X- ray of most patients with liver cirrhosis was normal (85%) (P value<0.05). There was a significant decrease in PaO2 and O2 saturation (P<0.001 for each) but a significant increase in P (A-a) O2 in patients with HPS versus cirrhotic patients (P<0.001). Patients with HPS showed a restrictive dysfunction in 59.3%. Conclusion: The prevalence of HPS among cirrhotic patients was 4.2%. The presence of dyspnea, platypnea, clubbing, orthodoxia and arterial hypoxemia were the commonest feature. Right pleural effusion and bilateral basal shadows were the commonest radiological findings.

A case of hepatopulmonary syndrome solved by mycophenolate mofetil (an inhibitor of angiogenesis and nitric oxide production)

The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multisystemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation and autoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multisystemic cases; so far there has been no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment. A teenage boy, diagnosed with ALPS at 4years of age (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13years of age, when he developed insidious hypoxemia (PaO 2 =46.7mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intrapulmonary shunt=45%). He was treated with oxygen (maximum 6L/min), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except for the pulmonary symptoms, therefore, after evaluation in referral centers in England, OLT was proposed. Since he was to undergo major surgery, sirolimus, which has wound-healing problems, was switched to mycophenolate mofetil (MMF). Following this change, we observed a huge improvement in pulmonary symptoms and reduction of oxygen needs. The intrapulmonary shunt decreased from 45% to 0% in less than a year, and it has not changed since (18months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year, lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation. The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in HPS pathogenesis). Therefore, we propose to perform clinical trials with MMF, and/or other angiogenesis and NO inhibitors, on a long-term treatment basis, to confirm their potential as a valid alternative to medical treatment of HPS.